Significance of early biopsy in pediatric kidney transplantation

Long-term renal allograft survival is limited mainly by the progressive process termed chronic allograft nephropathy (CAN) or chronic rejection. A pathological feature of CAN is characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta(1) plays an important role in fibrogenesis. We investigated whether the degree of TGF-beta(1) expression in early biopsy specimens routinely obtained from stable allografts at 100 days could predict fibrosis and graft dysfunction in the late phase by immunohistochemistry. Patients were children with a graft from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta(1) in the graft at 100 days using LC antibody (LC) for intracellular TGF-beta(1) and CC antibody (CC) for extracellular TGF-beta(1). We used the change in creatinine clearance between 100 days and 3 years after transplantation (Delta Ccr) as an index of long-term graft function. Image analysis was used to calculate the relative area involved by interstitial fibrosis in trichrome-stained sections of graft biopsy specimens at 100 days and 3 years, designating the change as Delta FI. Delta Ccr was - 4.2 +/- 9.4 mL/min in subjects with minimal early immunoreactivity for CC and - 20.5 +/- 5.9 mL/min in subjects with strong reactivity (p < 0.05). Delta Ccr was - 14.5 +/- 18.6 mL/min in subjects with minimal early immunoreactivity for LC and - 11.7 +/- 12.8 mL/min in those with strong reactivity. Delta FI in subjects with minimal CC reactivity (1.28 +/- 4.11 %) tended to be lower than in subjects with strong reactivity (8.45 +/- 15.47 %). Neither fibrosis at 100 days nor Delta FI differed between subjects with minimal and strong LC reactivity. Thus, extracellular TGF-beta(1) expression in grafts at 100 days after transplantation has an influence on long-term graft function and tends to be associated with increased graft fibrosis at 3 years.